title: DNA-binding activity of wild-type p53 protein is mediated by the central part of the molecule and controlled by its C terminus.
abstract: The DNA binding activity of wild type p53 is central to its activity. The "central" part of the molecule, where most mutations appear in primary human tumors, is the actual DNA binding domain. The C-terminal part was shown to exert a negative effect on the DNA binding activity. In the present study we show that while anti-p53 antibodies recognizing the C terminus of the wild type p53 facilitate DNA binding activity, blocking of the wild type specific epitope by specific anti-p53 antibodies, inhibited the DNA binding activity of the wild type p53 protein. An alternatively spliced p53 protein exhibits an augmented DNA binding activity. The fact that most p53 mutants have lost the wild type p53 conformation specific epitope, coupled with the observation that blocking of this site by binding specific antibodies, prevents the interaction of wild type p53 with DNA, suggests that maintaining the correct structural conformation of this site is central for DNA binding activity. Still, the internal structure of the p53 target and particularly the length of the sequence between the two tandem inverted repeats, is critical for protein-DNA interaction behavior.
authors.affiliation: Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Wolkowicz
authors.forename: A
authors.initials: A
authors.lastname: Peled
authors.forename: N B
authors.initials: NB
authors.lastname: Elkind
authors.forename: V
authors.initials: V
authors.lastname: Rotter
mesh_terms: D000911:Antibodies, Monoclonal; D001665:Binding Sites; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism*; D018076:DNA, Complementary; D000939:Epitopes; D006801:Humans; D011233:Precipitin Tests; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D000939:Epitopes; D016159:Tumor Suppressor Protein p53; D004247:DNA